ArticleJCI insight2023
Islet-autoreactive CD4+ T cells are linked with response to alefacept in type 1 diabetes.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 25 citations in OpenAlex.
- Immune dysregulation and stem-like CD8+ T cell enrichment in type 1 diabetes pancreatic lymph nodes.The Journal of clinical investigation · 2026Article
- Toward Personalized Medicine in Type 1 Diabetes: Understanding How Patient Heterogeneity Influences Therapeutic Efficacy.Diabetes, obesity & metabolism · 2026Review
- Teplizumab treatment for stage 2 type 1 diabetes: a real-world evaluation of metabolic and immunological outcomes.Diabetologia · 2026Observational
- Aberrant immune regulation and enrichment of stem-like CD8bioRxiv : the preprint server for biology · 2026Article
- Decoding autoimmune disease with single-cell immune repertoire and transcriptome sequencing: mechanisms and therapeutic opportunities.Frontiers in immunology · 2026Review
- A microenvironment-driven HLA-II-associated insulin neoantigen elicits persistent memory T cell activation in diabetes.Nature immunology · 2026Article
- Modulating immune response for the prevention and treatment of type 1 diabetes.Frontiers in immunology · 2026Review
- Aberrant IL-21/STAT3 signaling disrupts regulatory T cell function and CD4Frontiers in immunology · 2026Article
- Article
- Preclinical Diagnosis of Type 1 Diabetes: Reality or Utopia.Biomedicines · 2025Review
- The Mediation of Circulating Inflammatory Proteins in the Causal Pathway From Immune Cells to Delirium.Brain and behavior · 2025Article
- T cell and autoantibody recognition of nucleus-associated islet autoantigens in individuals with type 1 diabetes.Diabetologia · 2025Article
- Immunosuppressive agents in diabetes treatment: Hope or despair?World journal of diabetes · 2025Review
- Immunotherapies for prevention and treatment of type 1 diabetes.Immunotherapy · 2025Review
- Early expansion of TIGIT+PD1+ effector memory CD4 T cells via agonistic effect of alefacept in new-onset type 1 diabetes.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Single-cell RNA sequencing in studies of type 1 diabetes mellitus: modern state-of-the-art and technical peculiarities.Frontiers in endocrinology · 2025Review
- GM-CSFTheranostics · 2025Review
- Article
- Decoding the Significance of Alpha Cell Function in the Pathophysiology of Type 1 Diabetes.Cells · 2024Review
- Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Variation in the preservation of β cell function in clinical trials in type 1 diabetes (T1D) has emphasized the need to define biomarkers to predict treatment response. The T1DAL trial targeted T cells with alefacept (LFA-3-Ig) and demonstrated C-peptide preservation in approximately 30% of new-onset T1D individuals. We analyzed islet antigen-reactive (IAR) CD4+ T cells in PBMC samples collected prior to treatment from alefacept- and placebo-treated individuals using flow cytometry and single-cell RNA sequencing. IAR CD4+ T cells at baseline had heterogeneous phenotypes. Transcript profiles formed phenotypic clusters of cells along a trajectory based on increasing maturation and activation, and T cell receptor (TCR) chains showed clonal expansion. Notably, the frequency of IAR CD4+ T cells with a memory phenotype and a unique transcript profile (cluster 3) were inversely correlated with C-peptide preservation in alefacept-treated, but not placebo-treated, individuals. Cluster 3 cells had a proinflammatory phenotype characterized by expression of the transcription factor BHLHE40 and the cytokines GM-CSF and TNF-α, and shared TCR chains with effector memory-like clusters. Our results suggest IAR CD4+ T cells as a potential baseline biomarker of response to therapies targeting the CD2 pathway and warrant investigation for other T cell-related therapies.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.